Why do cells replicate?
To grow and reproduce
Cell division in Bacteria
- Is called Binary fission.
- Genome replicated early
- Copying of DNA circle occurs at replication origin
- This process needs energy [battery] from enzymes
- results in 2 side by side DNA circles on membrane
- Exists as double stranded circle of DNA
- Attached to one point on the interior of the cell membrane
- The Cell division Initiated by Growth of the Cell to a Certain Size
- New plasma membrane and cell wall materials laid down
- Growing membrane pinches inward, cell constricted in two
- Each cell contains a copy of the genome
Cell division in Eukaryotes
- Eukaryotic genome is larger and more complex than a bacterial genome.
- DNA in eukaryotes is within linear chromosomes.
- DNA forms a complex with histone proteins and is tightly coiled.
What are Chromosomes?
Chromosomes?
- DNA stores in Eukaryotes.
- They were first observed in dividing salamander larvae cells
- Number varies with species
- Chromosomes are composed of chromatin.
- Chromosomes contain some RNA since RNA is synthesised from DNA.
- The DNA exists as a long double-stranded fibre. That coils around histone polypeptides every 200 nucleotides. Resembles a string of beads.
- Nucleosome is a core that is formed by 8 histones.
- DNA is negatively charged and histones are positively charged, opposites attract.
- String of nucleosomes further wrapped into supercoils
Euchromatin vs Heterochromatin
- Heterochromatin = Highly condensed portions of chromatin. Some portions permanently condensed to prevent DNA expression.
- Euchromatin = Remainder of chromatin condensed ONLY DURING CELL REPLICATION. Movement of chromosomes facilitated by packaging. DNA is uncondensed to allow for gene expression.
Chromosome Karyotype
- Chromosomes differ widely in appearance
- Vary in size and shape and the location of the centromere (constriction), length of two arms and position of constricted regions
- The array of chromosomes a person possesses is called a karyotype.
- Karyotypes are different between species and sometimes even between individuals of the same species.
How many Chromosomes in a cell?
- All human body cells are Diploid. Have 23 Pairs of chromosomes. [2*23 =46]
- Pairs are called Homologues, as they are nearly identical.
- Human gametes have haploid complement with 23 chromosomes. [just 23]
- Before division each of the two homologues replicates
- They produce two identical copies called sister chromatids
- Chromatids remain joined together at the centromere
- Cells have 46 replicated chromosomes each with two chromatids.
- Possess 46 centromeres
- Four sets of genetic material: 23 pairs x 2 chromatids each
- Number of chromosomes indicated by number of centromere
The Cell Cycle
- This is a cycle of growth and division which has 5 stages.
- Interphases = g1, s, g2 phases
- Mitosis = M
- Cytokinesis = C
These make up the interphase
G1, S, G2 phases
G1 Phase
- Primary growth phase
- Encompasses major portion of cells lifespan.
S Phase
- Genome replica synthesis.
G2 Phase
- Preparation made for genomic separation.
- replication of mitochondria and other organelles
- chromosome condensation
- restructuring of microtubules and assembly at spindle
Mitosis- M Phase
- Microtubular apparatus assembled – Sister chromatids move apart from one another
Cytokinesis- C phase
- Physical division of the cell, creates two daughter cells
- Animal spindle helps position contracting cleavage furrow actin ring
What is the duration of the cell cycle?
- Variable durations
- Embryos exhibit shortest cycles
> Divide as quickly as DNA can be replicated
> Half of cycle is S, half is M, virtually no G1 or G2 - Mature cells have longer cycles
> Mammalian cell cycle averages 24 hours
> Growth occurs during G1 and G2
> G phases may be referred to as gap phases
> They separate the S phase from the M phase - M phase takes only small portion of cycle
- Length of cycle variability is in G1
- Many cells pause in a G0 resting stage
> May remain there for days to years, some remain permanently
> Most body cells are in G0 at any one time - Injury may stimulate some cells to enter G1 from G0.
Interphase
G1, S and G2
- G1 phase: cells undergo major portion of growth
- S phase: chromosome replicates to produce sister chromatids. Remain attached at the centromere. Specific DNA sequence bound to a protein kinetochore. Location specific to each chromosome
- G2 phase: chromosomes begin process of condensation. Motor proteins involved in rapid, final condensation. In G2 cells assemble machinery used to move chromosomes apart. Animals replicate centriole, nuclear microtubule-organizing centres. Eukaryotic cells synthesize tubulin, microtubule protein component.
Prophase
- Formation of the Mitotic Apparatus
> Chromosome condensation initiated in G2 continues. When chromosomes become visible through a light microscope, the first stage of mitosis has begun.
Ribosomal RNA synthesis ceases, nucleolus disappears
Microtubule apparatus made of spindle fibres begins to assemble
In animal cells the two centrioles move apart. Spindle apparatus, a bridge of microtubules, forms between them [the centrioles]
Position of spindle microtubules determines plane of cell division
Division occurs at right angles through the spindle
< Nuclear envelope breaks down, materials absorbed by ER
< Animal cells form an arrangement called an aster.
< Centrioles at opposite poles extend radial array of microtubules which functions to stiffen point of microtubular attachment.
< Second group of microtubules grow out from centromeres to poles
< Each chromosome possesses two kinetochores. Two sets of microtubules extend from each chromosome
< Kinetochore of each sister chromatid connected to one pole. Microtubules grow until they make contact with poles. Sister chromatids won’t separate if both connected to same pole.
Metaphase
- Division of the centromeres
Division of the Centromeres: Metaphase - Begins when pairs of sister chromatids align in centre of the cell
- Chromosomes align along the metaphase plate. [Not a physical structure]
- Indicates where future axis of cell division occurs.
- Centromeres are equidistant from each pole.
- Centromeres divide at the end of metaphase
- Centromere splits in two
- All centromeres divide in synchrony [same time]
Anaphase
- Separation of the Chromatids
Separation of the Chromatids: Anaphase
- Shortest phase, during which sister chromatids separate
- Chromatid drawn to pole to which it is attached
- Separation achieved by two simultaneous microtubular actions
- Poles move apart. • Microtubular spindle fibres slide past one another
- Microtubules are anchored at poles which are pushed apart
- Chromatids attached to poles move apart as well. Centromeres move toward poles
- Shortening process is not a contraction. Microtubules shorten as tubulin subunits are removed.
- Chromatids are therefore pulled toward poles.
Telophase
- Reformation of nuclei
Separation of chromatids completes partitioning of replicated genome
• Spindle apparatus is disassembled
• Tubulin units of microtubules are used to build new cytoskeleton
• Nuclear envelope re-forms around each new set of chromosomes
• Chromosomes begin to uncoil to allow gene expression
• rRNA genes begin transcription, nucleolus reappears
Cytokinesis
- Physical separation of the cell into two
Mitosis Complete at End of Telophase
• Replicated genome divided into two new nuclei at opposite ends of cell
• Cytoplasmic organelles assort to regions that will become separated
• Cleavage of the cell into two halves constitutes cytokinesis
• Cell is pinched in two by a constricting belt of microfilaments
• Actin filaments slide past one another
• Produces distinct cleavage furrow around circumference of cell
• Furrow deepens until the cell is literally pinched in two
Control of the cell cycle
- Events of Cell Cycle Coordinated Similarly in All Eukaryotes
- Little change in processes over billions of years
- Human proteins can function when transferred to yeast cell
- General Strategy of Cell Cycle Control – Goal of control is to optimize duration of cycle – Internal clock control cannot provide sufficient flexibility
- Eukaryotes use a centralized controller based on cellular feedback
- Analogy: furnace heating a house = At points in cycle feedback determines if cycle continues or is delayed
- Three principle check points
- Cell growth assessed at G1 check point • Called START in yeasts • If conditions favourable cell starts copying DNA, starting S phase
- DNA replication assessed at G2 check point
- Mitosis assessed at M check point
Molecular Mechanisms of cell cycle control
- Associated with interactions of proteins sensitive to cell conditions
- Cyclin-dependent protein kinases (Cdk’s)
- These enzymes phosphorylate serine and threonine of certain proteins
- Eg .Histones, nuclear membrane filaments, microtubule proteins at G2
- Cyclins –> Bind to Cdk’s, enable them to act as enzymes –mitosis promoting factor
- Are destroyed and resynthesized at each turn of cell cycle.
Growth factors and cell cycle
- Growth factors trigger intracellular signalling systems
- Example: fibroblasts
- Possess membrane receptors for platelet-derived growth factor, PDGF
- Binding PDGF and receptor initiates amplifying chain of events
- Tissue injury causes release of PDGF to promote healing
- Isolation of fifty growth factor proteins
- Each factor specifically recognized by specific cell surface receptor
- Some affect broad range of cell types, PDGF and E (epidermal) GF
- Some affect only certain cell types, N (nerve) GF and erythropoietin
- Cells deprived of growth factors stop at G1 , stay in G0.
